Carrageenan-induced inflammation in rat pleural cavity was used as a model to study how cellular activity is altered by anti-inflammatory drugs during the inflammatory response. In the early stages of the response, the pleural exudate contained a relatively high proportion of "mast cells" and high levels of intracellular histamine. As the inflammatory response developed, the mast cells were diluted by infiltration of large numbers of neutrophils. There was no evidence from studies with antihistamine drugs and the histamine liberator, Compound 48/80, that histamine was involved in this reaction. The total number of mast cells or total histamine content of the exudate did not decrease nor was there an increase in the levels of extracellular histamine. A significant increase in the numbers of neutrophils in the circulation accompanied the development of edema. This suggests that an important component of the inflammatory response was the mobilization of white cells from sources outside the circulation. Treatment with anti-inflammatory drugs produced a marked decrease (60-75%) in fluid volume and in the number of neutrophils in the exudate.